Juvenile Amyotrophic Lateral Sclerosis: A Review

Juvenile amyotrophic lateral sclerosis (JALS) is a rare group of motor neuron disorders with gene association in 40% of cases. JALS is defined as onset before age 25. We conducted a literature review of JALS and gene mutations associated with JALS. Results of the literature review show that the most common gene mutations associated with JALS are FUS, SETX, and ALS2. In familial cases, the gene mutations are mostly inherited in an autosomal recessive pattern and mutations in SETX are inherited in an autosomal dominant fashion. Disease prognosis varies from rapidly progressive to an indolent course. Distinct clinical features may emerge with specific gene mutations in addition to the clinical finding of combined upper and lower motor neuron degeneration. In conclusion, patients presenting with combined upper and lower motor neuron disorders before age 25 should be carefully examined for genetic mutations. Hereditary patterns and coexisting features may be useful in determining prognosis.

Peripartum Management of Patient with Long QT3 after Successful ICD Device Discharge Resulting in Device Failure: A Case Report

Background Long QT3 syndrome (LQT3) is a gain of function mutation of the SCN5A gene that is inherited in an autosomal dominant fashion. LQT3 results in an increase in arrhythmic events during rest, sleep, and bradycardia by extending the QT interval and inducing Torsades de pointes and sudden cardiac death. Attempting to block the sodium channel with Class I anti-arrhythmics or blocking adrenergic tone with beta blockers especially in women, have shown to be beneficial. There have been few large-scale studies on treating patients with LQT3 due to its lethality and underreported number of cases. Specifically, the safety and efficacy of pharmacologic treatment in pregnant LQT3 patients is unknown. Case summary This case demonstrates the safe use of Mexiletine and Propranolol in a third trimester pregnant LQT3 patient after a presumed ventricular arrhythmia and device-lead electrical short from therapy rendered her Implantable Cardioverter Defibrillator (ICD) inoperable in a VVI mode. With appropriate medications, the patient was safely monitored through the remainder of her pregnancy and safely delivered at 36 weeks of pregnancy a healthy baby girl. The daughter, heterozygous for LQT3, showed no evidence of intrauterine growth restriction or other side effects from the medications. Discussion There are many variants of the SCN5A gene mutations that can lead to different phenotypes and not all mutations are responsive to the same medications. In this case, Mexiletine and Propranolol, both of which have only recently shown to benefit certain variants or LQT3 respectively, were safely started during the third trimester of pregnancy without harming the fetus.

Intradural Extramedullary Lesions in Cervical Spine in Neurofibromatosis

Introduction: Neurofibromatosis (NF) is isolated into three diseases: NF type 1, type 2, and schwannoma. NF type 2 could be a disorder that's found roughly in 1/25,000–33,000 births with a mutation in gene 22q11.2, and it is passed through eras in an autosomal dominant fashion. Diagnosis is made with both clinical and radiological features. A few clinical features have been characterized in conclusion counting Manchester criteria. There is a scarce number of NF type 2 patients diagnosed with cervical lesions which are 25 in number. We report a case of an intradural extramedullary cervical lesion in a patient later diagnosed with NF type 2. Case Report: A 30-year-old male presenting with gradual onset and progressive course of spastic quadriparesis of six months’ duration was admitted through the emergency unit. MRI spine showed intradural extramedullary masses in the right side of C4 and left side of C6. The patient underwent cervical intradural excision of two masses under general anesthesia with neuromonitoring. The tumor was sent for histopathology and reported as NF type 2. Conclusion: NF is a common entity, but the diagnosis of cervical mass is judicious to avoid any complication in neurological function. It further needs a multidisciplinary approach and screening modalities.

A New Gene Mutation of PRKAR1A was found in a Carney Complex Case

Purpose Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare bilateral adrenocortical hyperplasia, inherited in an autosomal dominant fashion, resulting in a pro-adrenocorticotropic non-dependent Cushing's syndrome. PPNAD may be isolated or associated with Carney complex (CNC). For the diagnosis of PPNAD and CNC, a search for PRKAR1A mutations may be recommended in addition to hormonal and imaging tests. The purpose of this study was to investigate the clinical features, diagnosis and treatment of the new pathogenic mutations in the PRKAR1A gene causing Carney complex. Methods We report here a case of a patient whose clinical data were retrospectively analyzed. Results The 13-year-old patient was diagnosed with Carney complex through a series of tests and a new causative gene mutation locus (C.1-2942G>A) was identified. Conclusion Carney complex is usually more difficult to be diagnosed at an early stage in the clinic, and it is beneficial for clinicians to raise awareness of the disease for early recognition and timely intervention.

Identification of three novel homozygous variants in COL9A3 causing autosomal-recessive Stickler Syndrome

Background: Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelic COL9A3 variants reported to date. Results: Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants in COL9A3. Further, we have collected COL9A3 genotype-phenotype associations from the literature. Conclusion: Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders.

Recurrence of Avellino Corneal Dystrophy Following Penetrating Keratoplasty: A Case Report

Granular – lattice (Avellino) corneal dystrophy is inherited in an autosomal dominant fashion which affects stroma of the cornea with recurrent erosions and decreased vision due to clouding of cornea in later stage. We reported a case of 53-year old woman presented with pain and blurring of vision of left eye for 10 days with history of right eye deep anterior lamellar dystrophy and Left eye penetrating keratoplasty 5years back for Avellino dystrophy. On examination right eye graft was clear and left eye showed circular edges of irregular epithelium with patchy stains and epithelial defect suggestive of recurrence of dystrophy. A patient with recurrent corneal erosions and opacity in cornea has to be examined carefully so as not to overlook Avellino corneal dystrophy. Being a rare disorder this case has been reported to draw the attention of ophthalmologists about its recurrence following keratoplasty.

Foramina parietalia permagna: descrizione di un caso clinico e revisione della letteratura

The purpose of the present work is to expose the defects of parietal bone ossification and to identify the criteria for differential diagnosis and brain changes related to the condition, with particular attention to the venous developmental anomalies and the pathological features associated. Foramina parietalia permagna (FPP) are caused by an insufficient intramembranous ossification around the parietal notch that is normally obliterated in the fifth month of normal foetal development. During the first few years of life as calvarial growth continues, cranium bifidum tends to resolve into two distinct, large parietal foramina. Most people with FPP have a positive family history as the condition is inherited in an autosomal dominant fashion with high, but incomplete penetrance. Mutations of either MSX2 or ALX4 genes are associated with enlarged parietal foramina. Meningeal cortical vascular malformation of the straight sinus and persistent falcine sinus have also been reported in the literature as possible associated anomalies.

A presentation of hemiplegia and recurrent melena in Osler Weber Rendu syndrome

Osler Weber Rendu syndrome, synonymously Hereditary hemorrhagic telangiectasia, is a rare systemic disease with multiple-organ involvement. This genetic disorder inherits in an autosomal dominant fashion, with the incidence found closer to 1 in every 5,000 people. The condition can be diagnosed at any age and has an equal chance of affecting both males and females. A 74-year-old male, having a history of left hemiplegia, was admitted with a recent history of recurrent melena. An upper enteroscopy revealed bleeding telangiectasia in the proximal jejunum managed with hemoclips. The possibility of Osler Weber Rendu syndrome was considered as he developed bleeding recurrently. According to Curacao Criteria, a minimum of two out of four symptoms should be present to ratify the disease, and the presence of three symptoms makes a definite diagnosis. Since there is no cure for the syndrome to date, therapy's mainstay entails meticulous supportive care (focused on managing the manifestations). The disease is a type of arteriovenous malformation associated with the mutation in either endoglin (ENG) or activin A receptor-like kinase-1 (ACVRL1) genes. He was given an intraarticular injection of methotrexate in the left wrist hand because of small joint polyarthritis. The patient was symptomatically and clinically better on discharge. Novel treatment strategy includes bevacizumab and thalidomide though their use has not been clinically approved.

Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia

Non-coding RNAs (ncRNAs) are functional ribonucleic acid (RNA) species that include microRNAs (miRs), a class of short non-coding RNAs (∼21–25 nucleotides), and long non-coding RNAs (lncRNAs) consisting of more than 200 nucleotides. They regulate gene expression post-transcriptionally and are involved in a wide range of pathophysiological processes. Hereditary hemorrhagic telangiectasia (HHT) is a rare disorder inherited in an autosomal dominant fashion characterized by vascular dysplasia. Patients can develop life-threatening vascular malformations and experience severe hemorrhaging. Effective pharmacological therapies are limited. The study of ncRNAs in HHT is an emerging field with great promise. This review will explore the current literature on the involvement of ncRNAs in HHT as diagnostic and pathogenic factors.

Evaluation of Gene Variants in TGFB1, SERPINF1 and MEPE in a Spanish Family Affected by Otosclerosis and Tinnitus

Otosclerosis (OTSC) is a common type of deafness affecting up to 0.4 % of Caucasians. Its familial form is inherited in an autosomal dominant fashion, although to this date, no definitive cause for OTSC has been found. In the development of OTSC, three recent genetic association studies have suggested the participation of particular point mutations and small indels in the TGFB1, SERPINF1, and MEPE genes. Consequently, replicative studies are needed to confirm the role of the proposed mutations in OTSC patients. The goal of this study was to test the presence of the candidate variants described in the genes TGFB1, SERPINF1, and MEPE in a new case of familial OTSC with seven affected individuals. DNA was extracted from saliva samples of a Spanish family with several members affected by OTSC. PCR amplified target regions of some candidate genes, and the products were purified, Sanger-sequenced, and analyzed in silico. The family subject of the study did not carry the candidate variants for OTSC described in the genes TGFB1, SERPINF1, and MEPE, although it cannot be ruled out the involvement of other mutations in genes related to their same signaling pathways. This result highlights the importance of performing replicative studies for complex diseases, such as OTCS, in families of diverse origins. Additionally, a significant association of subjective tinnitus with OTSC has been found in this family, although the link between the two pathologies should be studied further.